Bowdensimon1324

Adult neurogenesis is well-described in the subventricular and subgranular zones of the mammalian brain. Recent observations that resident glia express stem cell markers in some areas of the brain not traditionally associated with neurogenesis hint to a possible role in tissue repair. The Bergmann glia (BG) population in the cerebellum displays markers and in vitro features associated with neural stem cells (NSC), however the physiological relevance of this phenotypic overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum. Here, this BG population was analysed in the adult cerebellum of different species and showed conservation of NSC-associated marker expression including Sox1, Sox2 and Sox9, in chick, primate and mouse cerebellum tissue. NSC-like cells isolated from adult mouse cerebellum showed slower growth when compared to lateral ventricle NSC, as well as differences upon differentiation. In a mouse model of cerebellar degeneration, progressive Purkinje cell loss was linked to cerebellar cortex disorganisation and a significant increase in Sox-positive cells compared to matching controls. EUK 134 mouse These results show that this Sox-positive population responds to cerebellar tissue disruption, suggesting it may represent a mobilisable cellular resource for targeted strategies to promote tissue repair.Dens invaginatus or dens in dente is a developmental dental anomaly resulting from an invagination of the enamel organ into the dental papilla during odontogenesis. Radiographically, it is usually seen as a radiolucent invagination surrounded by a radiopaque area (enamel) limited to the tooth crown or extending into the root. Because the invagination is opened to the oral cavity, it can retain saliva, food remnants, and bacteria. In conditions where the enamel lining of the invagination is naturally absent or lost because of caries, bacterial cells and products can diffuse from the invagination through the dentin tubules to reach the pulp and cause disease. Management of teeth with dens invaginatus includes preventive sealing or filling of the invagination, or if the pulp is affected, therapeutic options include vital pulp therapy, nonsurgical root canal treatment, apexification or regenerative endodontic procedures, periradicular surgery, intentional replantation, or extraction. It is recommended that the invagination be always approached, regardless of the type of dens invaginatus. The root canal should be treated whenever the pulp is irreversibly inflamed or necrotic. Endodontic management of teeth with dens invaginatus is often tricky because of its anatomic complexity, and special and customized strategies should be devised. This review discusses the endodontic implications of this anomaly and the current treatment recommendations based on anatomic, pathological, and technologic considerations.

To evaluate the distance from critical pelvic structures (CPS, defined as bladder and iliac vessels) among inflatable penile prosthesis (IPP) reservoirs placed into the space of Retzius (SOR) and high submuscular (HSM) locations using cross-sectional imaging. IPP reservoir placement into the HSM location has been proposed as a strategy to prevent injury due to greater distance from CPS.

Our institutional database was retrospectively reviewed to identify men who underwent IPP insertion between 2007 and 2020 and had available cross-sectional abdominopelvic imaging after the time of surgery. Patients were grouped based on reservoir placement technique (SOR vs. HSM). Staff radiologists blinded to placement technique evaluated reservoir position to determine the shortest distance between CPS and the reservoir and if a mass effect was present on CPS. Variables were analyzed using chi-squared, Fisher's exact, and student's T-tests as indicated.

Among 1,010 IPP cases performed during the study interval, 139 (13%) were imaged. Compared with SOR reservoirs (n=32), HSM reservoirs (n =107) were significantly less likely to induce a mass effect on the bladder (72 vs. 9%, P=<.01) or iliac vessels (34 vs. 4%, P=<.01) and were located roughly 5 times further from the bladder (10 ± 22 vs. 49 ± 36 mm, P=<.01) and iliac vessels (5 ± 9 vs. 23 ± 26 mm, P=<.01).

This study radiographically confirms that IPP reservoirs are located significantly further away from CPS following HSM placement compared to SOR placement.

This study radiographically confirms that IPP reservoirs are located significantly further away from CPS following HSM placement compared to SOR placement.Dyslipidemia or its severe version like familial hypercholesterolemia causes a high risk for cardiovascular diseases. Lomitapide, a microsomal triglyceride transfer protein inhibitor, is approved to treat familial hypercholesterolemia, associated with liver fat accumulation. In this work, we investigated the effect of the combination of lomitapide and triiodothyronine (T3) in Zucker fatty rats. Lomitapide (1 mg/kg, PO), or T3 (13 μg/kg, PO), or their combination, were given to these rats once daily for fourteen days. Body weight and food intake were recorded once daily during the treatment period. Serum and hepatic lipids, glucose tolerance, serum aminotransferases, bile fluids, hepatic gene expression, and liver histology were assessed at the end of the treatment. Lomitapide treatment reduced body weight, food intake, glucose intolerance, and serum lipids, and elevated serum aminotransferases and liver lipids. When combined with T3, lomitapide showed an enhanced reduction in body weight, food intake, serum cholesterol, serum LDL, and glucose intolerance. The combination treatment increased bile flow rate and biliary cholesterol excretion rate. Combining T3 with lomitapide attenuated the elevation of serum aminotransferases and liver lipids. Hepatic ABCB11, ABCG5, ABCG8, CYP7A1, CPT1, and ACOX1 expressions were increased with combination treatment. Histological analysis indicated that T3 attenuated hepatic fat accumulation caused by lomitapide. These data suggests that combining lomitapide with T3 may reduce lomitapide-induced hepatic toxicity and provide additional benefits in obesity and glucose intolerance.The tetrameric adaptor protein AP-3 is critical for the transport of proteins to lysosomes and lysosome-related organelles. The structures of homologous adaptors AP-1 and AP-2 have revealed a closed-to-open conformational change upon membrane recruitment and phosphoinositide binding. Recently, Schoppe et al. reported the first cryo-EM structures of AP-3 from budding yeast and described remarkably flexible solution structures that are all in the open conformation. The apparent lack of a closed conformational state, the first such description in the literature, allows AP-3 to be more reliant on cargo interaction for its initial membrane recruitment compared with AP-1.Neuropathic pain is the most common symptom for which patients seek medical attention. Existing treatments to control pain are largely ineffective because of poor understanding the underlying mechanisms. Synaptic plasticity is fundamental to the spinal sensitivity of neuropathic pain. In the present study, we showed that SNL induced significant allodynia and hyperalgesia as well as upregulation of Nwd1 and GluN2B, which were reversed by knockdown of NWD1. Electrophysiological experiments demonstrated that SNL enhanced synaptic transmission, which was prevented by knockdown of NWD1. In vitro experiments showed that knockdown of NWD1 inhibited dendritic growth and synaptogenesis. Taken together, our results suggest that NWD1 enhances synaptic transmission and contributes to the development of neuropathic pain by enhancing GluN2B synaptic expression and anchor and promoting excitatory synaptogenesis.Alterations in the nutritional environment in early life can significantly increase the risk for obesity and a range of development of metabolic disorders in offspring in later life, effects that can be passed onto future generations. This process, termed development programming, provides the framework of the developmental origins of health and disease (DOHaD) paradigm. Early life nutritional compromise including undernutrition, overnutrition or specific macro/micronutrient deficiencies, results in a range of adverse health outcomes in offspring that can be further exacerbated by a poor postnatal nutritional environment. Although the mechanisms underlying programming remain poorly defined, a common feature across the phenotypes displayed in preclinical models is that of altered wiring of neuroendocrine circuits that regulate satiety and energy balance. As such, altered maternal nutritional exposures during critical early periods of developmental plasticity can result in aberrant hardwiring of these circuits with lasting adverse consequences for the offspring. There is also increasing evidence around the role of an altered epigenome and the gut-brain axis in mediating some of the central programming effects observed. Further, although such programming was once considered to result in a permanent change in developmental trajectory, there is evidence, at least from preclinical models, that programming can be reversed via targeted nutritional manipulations during early development. Further work is required at a mechanistic level to allow for identification for early markers of later disease risk, delineation of sex-specific effects and pathways to implementation of strategies aimed at breaking the transgenerational transmission of disease.The 'apple-shaped' anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain, such as diabetes and hypertension. However, distinguishing between the consequences of visceral obesity, as opposed to visceral adiposity-associated metabolic and cardiovascular pathologies, presents certain challenges. This review summarizes current literature on relationships between adipose tissue distribution and cognition in preclinical models and highlights unanswered questions surrounding the potential role of tissue- and cell type-specific insulin resistance in these effects. While gaps in knowledge persist related to insulin insensitivity and cognitive impairment in obesity, several recent studies suggest that cells of the neurovascular unit contribute to hippocampal synaptic dysfunction, and this review interprets those findings in the context of progressive metabolic dysfunction in the CNS. Signalling between cerebrovascular endothelial cells, astrocytes, microglia, and neurons has been linked with memory deficits in visceral obesity, and this article describes the cellular changes in each of these populations with respect to their role in amplification or diminution of peripheral signals. The picture emerging from these studies, while incomplete, implicates pro-inflammatory cytokines, insulin resistance, and hyperglycemia in various stages of obesity-induced hippocampal dysfunction. As in the parable of the five blind wanderers holding different parts of an elephant, considerable work remains in order to assemble a model for the underlying mechanisms linking visceral adiposity with age-related cognitive decline.